Mucus is a viscous and adhesive substance that efficiently traps and removes pathogens, hazard particles, and conventional drug or gene carriers from mucosal surfaces, including those that cover the female reproductive tract, GI tract, lung, airway and eyes. To deliver therapeutics efficiently across the mucosal surfaces, drug or gene carriers must be able to penetrate the mucus barrier to avoid the mucus-induced aggregation and rapid clearance.
Different strategies have been proposed to render drug or gene carriers muco-inert by covalently or non-covalently modifying particle surfaces with a dense coating of low molecular weight (MW) poly(ethylene glycol) (PEG), a hydrophilic, neutrally charged molecule that efficiently shields particles from strong adhesion to mucus. Prior formulations of mucus-penetrating particles (MPP) are mainly based on biodegradable polymers, of which the hydrophobic segment serves as the loading vehicle for poorly soluble drugs. However, it remains challenging to encapsulate water soluble agents (e.g, proteins such as antibodies or growth factors) in hydrophobic polymeric particles, especially for those with small sizes at sub-micron scale such as MPP.
Lipid-based systems, such as liposomes, have been studied as means for effective drug delivery, particularly for hydrophilic or water-soluble agents. However, these systems are generally unable to achieve efficient transmucosal delivery mainly due to the strong hindrance by the mucus mesh. The intense interactions between delivery particles and mucus constituents might also induce unwanted decomposition of the particles or the encapsulated payloads.
There exists a need for a drug delivery systems which can rapidly penetrate mucus which overcomes the limitations discussed above associated with polymeric systems.
Therefore, there is a need to provide a drug delivery system, particularly a lipid-based system, such as liposomes, which can rapidly penetrate mucus which overcomes the limitations discussed above associated with polymeric systems and methods of making and using thereof.